Reference SummaryMarsh V, Nat Genet 2008 Dec;40(12):1436-44

Title

Epithelial Pten is dispensable for intestinal homeostasis but suppresses adenoma development and progression after Apc mutation.

Authors

Marsh V; Winton DJ; Williams GT; Dubois N; Trumpp A; Sansom OJ; Clarke AR

Journal

Nat Genet

Volume

40

Issue

12

Year

2008

Pages

1436-44

Abstract

PTEN acts as a tumor suppressor in a range of tissue types and has been implicated in the regulation of intestinal stem cells. To study Pten function in the intestine, we used various conditional transgenic strategies to specifically delete Pten from the mouse intestinal epithelium. We show that Pten loss specifically within the adult or embryonic epithelial cell population does not affect the normal architecture or homeostasis of the epithelium. However, loss of Pten in the context of Apc deficiency accelerates tumorigenesis through increased activation of Akt, leading to rapid development of adenocarcinoma. We conclude that Pten is redundant in otherwise normal intestinal epithelium and epithelial stem cells but, in the context of activated Wnt signaling, suppresses progression to adenocarcinoma through modulation of activated Akt levels.

Links

J:143082 – Mouse Genome Informatics
19011632 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
[not specified]-Apctm1Tno/+ Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine adenocarcinoma
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

observed

[not specified]-Apctm1Tno/+ Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine adenocarcinoma
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

observed

[not specified]-Apctm1Tno/+ Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine adenoma
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

observed

[not specified]-Apctm1Tno/+ Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine adenoma
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

observed

[not specified]-Apctm1Tno/+ Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine adenoma - dysplastic
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

observed

[not specified]-Apctm1Tno/+ Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine adenoma - intramucosal
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

observed

[not specified]-Apctm1Tno/+ Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine adenoma - microadenoma
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

observed

[not specified]-Apctm1Tno/+ Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine adenoma - microadenoma
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

observed

[not specified]-Apctm1Tno/+ Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine lesion
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

observed - 94.74

[not specified]-Apctm1Tno/+ Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine lesion - polypoid
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

33.33

[not specified]-Apctm1Tno/+ Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine polyp
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

58.33

[not specified]-Apctm1Tno/+ Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine tumor
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

observed

[not specified]-Apctm1Tno/+ Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine tumor
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

observed

[not specified]-Ptentm2Mak Tg(Vil1-cre/ERT2)23Syr Intestine hamartoma
  • tamoxifen (For inducing expression from mutant alleles)
Intestine

0

[not specified]-Tg(Cyp1a1-cre/ERT)1Dwi Intestine hamartoma
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine

0

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine hamartoma
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine

0

[not specified]-Gt(ROSA)26Sortm1Sor Ptentm2Mak Tg(Cyp1a1-cre)1Dwi Intestine lesion - hamartomatous
  • beta-naphthoflavone (betaNF)
Intestine

0

[not specified]-Gt(ROSA)26Sortm1Sor Ptentm2Mak Intestine lesion - hamartomatous
  • beta-naphthoflavone (betaNF)
Intestine

0

[not specified]-Gt(ROSA)26Sortm1Sor Tg(Cyp1a1-cre)1Dwi Intestine lesion - hamartomatous
  • beta-naphthoflavone (betaNF)
Intestine

0

[not specified]-Gt(ROSA)26Sortm1Sor Ptentm2Mak/+ Tg(Cyp1a1-cre)1Dwi Intestine lesion - hamartomatous
  • beta-naphthoflavone (betaNF)
Intestine

0

[not specified]-Gt(ROSA)26Sortm1Sor Ptentm2Mak/+ Intestine lesion - hamartomatous
  • beta-naphthoflavone (betaNF)
Intestine

0

[not specified]-Tg(Cyp1a1-cre/ERT)1Dwi Intestine tumor
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine

0

[not specified]-Gt(ROSA)26Sortm1Sor Ptentm2Mak Tg(Cyp1a1-cre)1Dwi Leukocyte lymphoma
  • beta-naphthoflavone (betaNF)
Leukocyte

observed

[not specified]-Gt(ROSA)26Sortm1Sor Ptentm2Mak Tg(Cyp1a1-cre)1Dwi Liver hepatocellular adenoma
  • beta-naphthoflavone (betaNF)
Liver

observed

[not specified]-Gt(ROSA)26Sortm1Sor Ptentm2Mak Tg(Cyp1a1-cre)1Dwi Uterus - Endometrium hyperplasia - atypical - complex
  • beta-naphthoflavone (betaNF)
Uterus - Endometrium

observed